Exploring the role of anticipatory postural adjustment duration within APA2 subphase as a potential mediator between clinical disease severity and fall risk in Parkinson's disease.

Introduction: People with Parkinson's Disease (PD) often show reduced anticipatory postural adjustments (APAs) before voluntary steps, impacting their stability. The specific subphase within the APA stage contributing significantly to fall risk remains unclear. Methods: We analyzed center of pressure (CoP) trajectory parameters, including duration, length, and velocity, throughout gait initiation. This examination encompassed both the postural phase, referred to as anticipatory postural adjustment (APA) (APA1, APA2a, APA2b), and the subsequent locomotor phases (LOC). Participants were instructed to initiate a step and then stop (initiating a single step). Furthermore, we conducted assessments of clinical disease severity using the Unified Parkinson's Disease Rating Scale (UPDRS) and evaluated fall risk using Tinetti gait and balance scores during off-medication periods. Results: Freezing of gait (FOG) was observed in 18 out of 110 participants during the measurement of CoP trajectories. The Ramer-Douglas-Peucker algorithm successfully identified CoP displacement trajectories in 105 participants (95.5%), while the remaining 5 cases could not be identified due to FOG. Tinetti balance and gait score showed significant associations with levodopa equivalent daily dose, UPDRS total score, disease duration, duration (s) in APA2a (s) and LOC (s), length in APA1 (cm) and APA2b (cm), mediolateral velocity in APA1 (X) (cm/s), APA2a (X) (cm/s), APA2b (X) (cm/s) and LOC (X) (cm/s), and anterior-posterior velocity in APA2a (Z) (cm/s) and APA2b (Z) (cm/s). Multiple linear regression revealed that only duration (s) in APA2a and UPDRS total score was independently associated with Tinetti gait and balance score. Further mediation analysis showed that the duration (s) in APA2a served as a mediator between UPDRS total score and Tinetti balance and gait score (Sobel test, p = 0.047). Conclusion: APA2 subphase duration mediates the link between disease severity and fall risk in PD, suggesting that longer APA2a duration may indicate reduced control during gait initiation, thereby increasing fall risk.

Prediction of extranodal extension in head and neck squamous cell carcinoma by CT images using an evolutionary learning model.

BACKGROUND: Extranodal extension (ENE) in head and neck squamous cell carcinoma (HNSCC) correlates to poor prognoses and influences treatment strategies. Deep learning may yield promising performance of predicting ENE in HNSCC but lack of transparency and interpretability. This work proposes an evolutionary learning method, called EL-ENE, to establish a more interpretable ENE prediction model for aiding clinical diagnosis. METHODS: There were 364 HNSCC patients who underwent neck lymph node (LN) dissection with pre-operative contrast-enhanced computerized tomography images. All the 778 LNs were divided into training and test sets with the ratio 8:2. EL-ENE uses an inheritable bi-objective combinatorial genetic algorithm for optimal feature selection and parameter setting of support vector machine. The diagnostic performances of the ENE prediction model and radiologists were compared using independent test datasets. RESULTS: The EL-ENE model achieved the test accuracy of 80.00%, sensitivity of 81.13%, and specificity of 79.44% for ENE detection. The three radiologists achieved the mean diagnostic accuracy of 70.4%, sensitivity of 75.6%, and specificity of 67.9%. The features of gray-level texture and 3D morphology of LNs played essential roles in predicting ENE. CONCLUSIONS: The EL-ENE method provided an accurate, comprehensible, and robust model to predict ENE in HNSCC with interpretable radiomic features for expanding clinical knowledge. The proposed transparent prediction models are more trustworthy and may increase their acceptance in daily clinical practice.

Effectiveness of Center of Pressure Trajectory as Anticipatory Postural Adjustment Measurement in Parkinson's Disease With Freezing of Gait History.

BACKGROUND: Evidence showed that patients with Parkinson's disease (PD) who have a history of freezing of gait (FOG) have hypometric anticipatory postural adjustment (APA) during gait initiation (GI) compared to PD without FOG. OBJECTIVES: This study aimed to test the feasibility of center of pressure (COP) displacement during GI as the measure of APA in PD with and without a history of FOG. METHODS: Patients with PD underwent COP trajectory measurements, including duration, length, velocity, and acceleration in different phases of APA (APA1, APA2a, APA2, and LOC), as well as evaluation of New Freezing of Gait Questionnaire (NFOG-Q), Tinetti balance and gait score, and Postural Instability and Gait Difficulty (PIGD) score in the on and off medication states. RESULTS: The duration (seconds) of APA2a, APA2b, and LOC were highest while velocity in mediolateral direction (X) (m/s), including APA1, APA2a, APA2b, and LOC showed lowest in PD with FOG. Velocity in the mediolateral direction in different phases of APA increased in patients with FOG after dopaminergic therapy. APA2a (seconds) and APA2b (X) (m/s) were significantly associated with NFOG-Q part II, APA2b (X) (m/s) was significantly associated with NFOG-Q part III, and APA2a (seconds) was significantly associated with Tinetti balance and gait and PIGD score. CONCLUSIONS: PD with FOG history showed a favorable response of APAs to dopaminergic replacement. The APA parameters by COP trajectory, especially lateral COP shift toward the stance foot (APA2b (X) (m/s) and APA2a (seconds)) are surrogate markers to assess PD with FOG history.

Improving detection of impacted animal bones on lateral neck radiograph using a deep learning artificial intelligence algorithm.

OBJECTIVE: We aimed to develop a deep learning artificial intelligence (AI) algorithm to detect impacted animal bones on lateral neck radiographs and to assess its effectiveness for improving the interpretation of lateral neck radiographs. METHODS: Lateral neck radiographs were retrospectively collected for patients with animal bone impaction between January 2010 and March 2020. Radiographs were then separated into training, validation, and testing sets. A total of 1733 lateral neck radiographs were used to develop the deep learning algorithm. The testing set was assessed for the stand-alone deep learning AI algorithm and for human readers (radiologists, radiology residents, emergency physicians, ENT physicians) with and without the aid of the AI algorithm. Another radiograph cohort, collected from April 1, 2020, to June 30, 2020, was analyzed to simulate clinical application by comparing the deep learning AI algorithm with radiologists' reports. RESULTS: In the testing set, the sensitivity, specificity, and accuracy of the AI model were 96%, 90%, and 93% respectively. Among the human readers, all physicians of different subspecialties achieved a higher accuracy with AI-assisted reading than without. In the simulation set, among the 20 cases positive for animal bones, the AI model accurately identified 3 more cases than the radiologists' reports. CONCLUSION: Our deep learning AI model demonstrated a higher sensitivity for detection of animal bone impaction on lateral neck radiographs without an increased false positive rate. The application of this model in a clinical setting may effectively reduce time to diagnosis, accelerate workflow, and decrease the use of CT.

Clinical Utility of Plantar Pressure Measurements as Screening in Patients With Parkinson Disease With and Without Freezing of Gait History.

OBJECTIVE: To test the feasibility of objective assessments using the TekScan MatScan pressure mat plantar pressure measurement as a time-effective screening service for Parkinson disease (PD) with and without freezing of gait (FOG) history. DESIGN: Prospective cross-sectional study. SETTING: Largest medical center in southern Taiwan. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Plantar pressure measurements including average peak pressure (PP), contact area (CA), and pressure-time integral (PTI) in static and dynamic conditions as well as clinical scores during off-medication states. PARTICIPANTS: A total of 103 patients with PD and 22 age- and sex-matched volunteers without PD (N=125). RESULTS: Plantar pressure assessment including PP, CA, and PTI on the total foot areas between participants with PD and controls without PD in the static conditions are similar. Patients with PD presented higher PTI on total foot areas as well as hallux, midfoot area, and medial and lateral heels during dynamic conditions than controls without PD. The PP, CA, and PTI during the static condition and CA during the dynamic condition on the hallux showed statistical significance between PD with and without FOG history. Stepwise logistic regression after controlling with age and body mass index showed only PTI on hallux (static conditions) was significantly associated with the presence of FOG. The receiver operating characteristic curve analysis in diagnostic accuracy for FOG in PTI was statistically significant (P=.002; area under the curve, 0.71). CONCLUSIONS: FOG screening using the TekScan MatScan pressure mat plantar pressure measurement could serve as a time-effective screening service at the outpatient clinic. Based on our study, PTI may be valuable in auxiliary diagnosis.

Clinical Disease Severity Mediates the Relationship between Stride Length and Speed and the Risk of Falling in Parkinson's Disease.

The shuffling gait with slowed speed and reduced stride length has been considered classic clinical features in idiopathic Parkinson's disease (PD), and the risk of falling increases as the disease progresses. This raises the possibility that clinical disease severity might mediate the relationship between stride length and speed and the risk of falling in patients with PD. Sixty-one patients with PD patients underwent the clinical scores as well as quantitative biomechanical measures during walking cycles before and after dopamine replacement therapy. Mediation analysis tests whether the direct effect of an independent variable (stride length and speed) on a dependent variable (three-step fall prediction model score) can be explained by the indirect influence of the mediating variable (Unified Parkinson's Disease Rating Scale (UPDRS) total scores). The results demonstrate that decreased stride length, straight walking speed, and turning speed is associated with increased three-step fall prediction model score (r = -0.583, p < 0.0001, r = -0.519, p < 0.0001, and r = -0.462, p < 0.0001, respectively). We further discovered that UPDRS total scores value is negatively correlated with stride length, straight walking, and turning speed (r = -0.651, p < 0.0001, r = -0.555, p < 0.0001, and r = -0.372, p = 0.005, respectively) but positively correlated with the fall prediction model score value (r = 0.527, p < 0.0001). Further mediation analysis shows that the UPDRS total score values serve as mediators between lower stride length, straight walking, and turning speed and higher fall prediction model score values. Our results highlighted the relationship among stride length and speed, clinical disease severity, and risk of falling. As decreased stride length and speed are hallmarks of falls, monitoring the changes of quantitative biomechanical measures along with the use of wearable technology in a longitudinal study can provide a scientific basis for pharmacology, rehabilitation programs, and selecting high-risk candidates for surgical treatment to reduce future fall risk.

Brain CT can predict low lean mass in the elderly with cognitive impairment: a community-dwelling study.

BACKGROUND: The coexistence of sarcopenia and dementia in aging populations is not uncommon, and they may share common risk factors and pathophysiological pathways. This study aimed to evaluate the relationship between brain atrophy and low lean mass in the elderly with impaired cognitive function. METHODS: This cross-sectional study included 168 elderly patients who visited the multi-disciplinary dementia outpatient clinic at Kaohsiung Chang Gung Memorial Hospital for memory issues, between 2017 and 2019. The body composition was assessed by dual energy X-ray absorptiometry (DEXA) and CT based skeletal muscle index including L3 skeletal muscle index (L3SMI) and masseter muscle mass index (MSMI). The brain atrophy assessment was measured by CT based visual rating scale. Possible predictors of low lean mass in the elderly with cognitive impairement were identified by binary logistic regression. ROC curves were generated from binary logistic regression. RESULTS: Among the 81 participants, 43 (53%) remained at a normal appendicular skeletal muscle index (ASMI), whereas 38 (47%) showed low ASMI. Compared with the normal ASMI group, subjects with low ASMI exhibited significantly lower BMI, L3SMI, and MSMI (all p < 0.05), and showed significant brain atrophy as assessed by visual rating scale (p < 0.001). The accuracy of predictive models for low ASMI in the elderly with cognitive impairment were 0.875, (Area under curve (AUC) = 0.926, 95% confidence interval [CI] 0.844-0.972) in model 1 (combination of BMI, GCA and L3SMI) and 0.885, (Area under curve (AUC) = 0.931, [CI] 0.857-0.979) in model 2 (combination of BMI, GCA and MSMI). CONCLUSIONS: Global cortical atrophy and body mass index combined with either L3 skeletal muscle index or masseter skeletal muscle index can predict low lean mass in the elderly with cognitive impairment.

Feasibility of Combining Disease-Specific and Balance-Related Measures as Risk Predictors of Future Falls in Patients with Parkinson's Disease.

Evidence supports the view that postural sway in a quiet stance increases with clinical disease severity and dopaminergic therapy in idiopathic Parkinson's disease (PD), which, in turn, increases the risk of falling. This study evaluated the feasibility of combining disease-specific and balance-related measures as risk predictors for future falls in patients with PD. The patients with PD underwent postural sway measurements (area, length, and velocity traveled by the excursion of the center of pressure) and clinical functional scores (Parkinson's Disease Rating Scale [UPDRS] and Tinetti balance and gait score assessment) in both the on- and off-states of dopaminergic therapy. The outcome was defined as the development of a new fall. The sway area, velocity, and length increased after the medication administration. The Cox proportional hazards model showed that only previous fall history, Tinetti balance and gait score (on-state), and levodopa equivalent daily dose (LEDD) were associated with the development of future falls. The cumulative risk of fall development showed that the sway length and velocity were associated with future falls after more than six months. The combined LEDD, Tinetti balance and gait score (on-state), and velocity and length of postural sway (on-state) had the highest diagnostic accuracy (area under the curve = 0.9, p < 0.0001). Dopaminergic therapy can improve clinical functional scores but worsen balance-related measures. Increased sway length and velocity during the medication state are hallmarks of future falls, particularly in advanced PD. Combining disease-specific and balance-related measures can serve as an auxiliary diagnosis as risk predictors for future falls.

The Potential Effects of Oxidative Stress-Related Plasma Abnormal Protein Aggregate Levels on Brain Volume and Its Neuropsychiatric Consequences in Parkinson's Disease.

BACKGROUND: Oxidative stress has been implicated in the pathogenesis of many diseases, including Parkinson's disease. Large protein aggregates may be produced after the breakdown of the proteostasis network due to overt oxidative stress. Meanwhile, brain volume loss and neuropsychiatric deficits are common comorbidities in Parkinson's disease patients. In this study, we applied a mediation model to determine the potential influences of oxidative stress-related plasma abnormal protein aggregate levels on brain volume and neuropsychiatric consequences in Parkinson's disease. METHOD: 31 patients with PD and 24 healthy controls participated in this study. The PD patients were further grouped according to the presentation of cognitive decline or not. All participants received complete examinations to determine plasma abnormal protein aggregates levels, brain volume, and neuropsychiatric performance. The results were collected and analyzed in a single-level three-variable mediation model. RESULTS: Patients with PD cognitive decline exhibited higher plasma NfL levels, decreased regional brain volume, and poor neuropsychiatric subtest results compared with PD patients with normal cognition, with several correlations among these clinical presentations. The mediation model showed that the superior temporal gyrus completely mediated the effects of elevated plasma NfL levels due to the poor psychiatric performance of picture completion and digit span. CONCLUSION: This study provides insight into the effects of oxidative stress-related plasma abnormal protein aggregate levels on regional brain volume and neuropsychiatric consequences in Parkinson's disease patients.

Brain Atrophy Mediates the Relationship between Misfolded Proteins Deposition and Cognitive Impairment in Parkinson's Disease.

Parkinson's disease is associated with cognitive decline, misfolded protein deposition and brain atrophy. We herein hypothesized that structural abnormalities may be mediators between plasma misfolded proteins and cognitive functions. Neuropsychological assessments including five domains (attention, executive, speech and language, memory and visuospatial functions), ultra-sensitive immunomagnetic reduction-based immunoassay (IMR) measured misfolded protein levels (phosphorylated-Tau, Amyloidß-42 and 40, α-synuclein and neurofilament light chain) and auto-segmented brain volumetry using FreeSurfur were performed for 54 Parkinson's disease (PD) patients and 37 normal participants. Our results revealed that PD patients have higher plasma misfolded protein levels. Phosphorylated-Tau (p-Tau) and Amyloidß-42 (Aß-42) were correlated with atrophy of bilateral cerebellum, right caudate nucleus, and right accumbens area (RAA). In mediation analysis, RAA atrophy completely mediated the relationship between p-Tau and digit symbol coding (DSC). RAA and bilateral cerebellar cortex atrophy partially mediated the Aß-42 and executive function (DSC and abstract thinking) relationship. Our study concluded that, in PD, p-Tau deposition adversely impacts DSC by causing RAA atrophy. Aß-42 deposition adversely impacts executive functions by causing RAA and bilateral cerebellum atrophy.

Associations among Cognitive Functions, Plasma DNA, and Diffusion Tensor Image along the Perivascular Space (DTI-ALPS) in Patients with Parkinson's Disease.

BACKGROUND: Parkinson's disease (PD) is a common neurodegenerative disease associated with accumulation of misfolding proteins and increased neuroinflammation, which may further impair the glymphatic system. The purpose of this study was to utilize diffusion tensor image analysis along the perivascular space (DTI-ALPS) to evaluate glymphatic system activity and its relationship with systemic oxidative stress status in PD patients. METHODS: Magnetic resonance imaging and neuropsychological tests were conducted on 25 PD patients with normal cognition (PDN), 25 PD patients with mild cognitive impairment (PD-MCI), 38 PD patients with dementia (PDD), and 47 normal controls (NC). Oxidative stress status was assessed by plasma DNA level. Differences in ALPS-index among the subgroups were assessed and further correlated with cognitive functions and plasma DNA levels. RESULTS: The PD-MCI and PDD groups showed significantly lower ALPS-index compared to normal controls. The ALPS-index was inversely correlated with plasma nuclear DNA, mitochondrial DNA levels, and cognitive scores. CONCLUSIONS: Lower diffusivity along the perivascular space, represented by lower ALPS-index, indicates impairment of the glymphatic system in PD patients. The correlation between elevated plasma nuclear DNA levels and lower ALPS-index supports the notion that PD patients may exhibit increased oxidative stress associated with glymphatic system microstructural alterations.

The corticolimbic structural covariance network as an early predictive biosignature for cognitive impairment in Parkinson's disease.

Structural covariance assesses similarities in gray matter between brain regions and can be applied to study networks of the brain. In this study, we explored correlations between structural covariance networks (SCNs) and cognitive impairment in Parkinson's disease patients. 101 PD patients and 58 age- and sex-matched healthy controls were enrolled in the study. For each participant, comprehensive neuropsychological testing using the Wechsler Adult Intelligence Scale-III and Cognitive Ability Screening Instrument were conducted. Structural brain MR images were acquired using a 3.0T whole body GE Signa MRI system. T1 structural images were preprocessed and analyzed using Statistical Parametric Mapping software (SPM12) running on Matlab R2016a for voxel-based morphometric analysis and SCN analysis. PD patients with normal cognition received follow-up neuropsychological testing at 1-year interval. Cognitive impairment in PD is associated with degeneration of the amygdala/hippocampus SCN. PD patients with dementia exhibited increased covariance over the prefrontal cortex compared to PD patients with normal cognition (PDN). PDN patients who had developed cognitive impairment at follow-up exhibited decreased gray matter volume of the amygdala/hippocampus SCN in the initial MRI. Our results support a neural network-based mechanism for cognitive impairment in PD patients. SCN analysis may reveal vulnerable networks that can be used to early predict cognitive decline in PD patients.

Vascular Inflammation Is a Risk Factor Associated with Brain Atrophy and Disease Severity in Parkinson's Disease: A Case-Control Study.

INTRODUCTION: Systemic inflammation with elevated oxidative stress causing neuroinflammation is considered a major factor in the pathogenesis of Parkinson's disease (PD). The interface between systemic circulation and the brain parenchyma is the blood-brain barrier (BBB), which also plays a role in maintaining neurovascular homeostasis. Vascular cell adhesion molecule-1 (VCAM-1) and microRNAs (miRNAs) regulate brain vessel endothelial function, neoangiogenesis, and, in turn, neuronal homeostasis regulation, such that their dysregulation can result in neurodegeneration, such as gray matter atrophy, in PD. OBJECTIVE: Our aim was to evaluate the associations among specific levels of gray matter atrophy, peripheral vascular adhesion molecules, miRNAs, and clinical disease severity in order to achieve a clearer understanding of PD pathogenesis. METHODS: Blood samples were collected from 33 patients with PD and 27 healthy volunteers, and the levels of VCAM-1 and several miRNAs in those samples were measured. Voxel-based morphometry (VBM) analysis was performed using 3 T magnetic resonance imaging (MRI) and SPM (Statistical Parametric Mapping software program). The associations among the vascular parameter, miRNAs, gray matter volume, and clinical disease severity measurements were evaluated by partial correlation analysis. RESULTS: The levels of VCAM-1, miRNA-22, and miRNA-29a expression were significantly elevated in the PD patients. The gray matter volume atrophy in the left parahippocampus, bilateral posterior cingulate gyrus, fusiform gyrus, left temporal gyrus, and cerebellum was significantly correlated with increased clinical disease severity, the upregulation of miRNA levels, and increased vascular inflammation. CONCLUSION: Patients with PD seem to have abnormal levels of vascular inflammatory markers and miRNAs in the peripheral circulation, and these levels are correlated with specific brain volume changes. This study reinforces the associations among peripheral inflammation, the BBB interface, and gray matter atrophy in PD and further demonstrates that BBB dysfunction with neurovascular impairment may play an important role in PD progression.

Plasma Levels of α-Synuclein, Aß-40 and T-tau as Biomarkers to Predict Cognitive Impairment in Parkinson's Disease.

OBJECTIVE: In this study, we assessed plasma biomarkers to identify cognitive impairment in Parkinson's disease (PD) patients by applying ultra-sensitive immunomagnetic reduction-based immunoassay (IMR). METHODS: The study enrolled 60 PD patients and 28 age- and sex-matched normal controls. Complete cognitive function assessments were performed on participants using the Mini-Mental State Examination (MMSE) and Clinical Dementia Rating. PD patients with an MMSE score of ≦26 were defined as having cognitive impairment. Meanwhile, a 99mTc-TRODAT-1 scan was performed and plasma levels of Aß-40, Aß-42, T-tau, and α-synuclein were evaluated using IMR, subsequent correlation analyses were then performed. RESULTS: Compared with normal adults, PD patients have higher plasma levels of α-synuclein and T-tau, and a lower level of Aß-40 (p < 0.05). Plasma levels of α-synuclein (r = -0.323, p = 0.002), Aß-40 (r = 0.276, p = 0.01), and T-tau (r = -0.322, p = 0.002) are significantly correlated with MMSE scores. The TRODAT scan results, including visual inspection and quantification, revealed significant correlations between Aß-40 and PD. Multiple regression analysis showed that the plasma levels of Aß-40 (OR = 0.921, 95% CI = 0.879-0.962), α-synuclein (OR = 3.016, 95% CI = 1.703-5.339), and T-tau (OR = 1.069, 95% CI = 1.026-1.115) were independently associated with PD patients with cognitive impairment. The cutoff values for predicting cognitive deficits in PD patients were 45.101 pg/ml of Aß-40, (Area under curve (AUC) = 0.791), 0.389 pg/ml of α-synuclein, (AUC = 0.790), and 30.555 pg/ml of T-tau (AUC = 0.726). CONCLUSION: Plasma levels of α-synuclein, Aß-40, and T-tau are potential biomarkers to detect cognitive impairment in PD patients.

Associations between Brain Structural Damage and Core Muscle Loss in Patients with Parkinson's Disease.

BACKGROUND: Parkinson's disease (PD) is a common neurodegenerative disease associated with progressive gray matter atrophy. In addition to motor function disorder, frailty and decreased muscle mass potentially contribute to increased morbidity risk. OBJECTIVE: This study aimed to investigate the associations between lean muscle loss and gray matter volume (GMV) in PD patients. METHODS: Thirty patients with PD and fifteen healthy controls underwent brain and bilateral thigh MRIs. The IDEAL sequence was employed, measuring the regions of interest (ROI) of fat percentage at the 50% point of femur length. Voxel-base morphometry (VBM) was used to assess regional gray matter volume differences between groups. Further correlation analysis was performed to evaluate the changes between gray matter volume and fatty percentage of the bilateral thigh after adjusting for age and gender. Multiple linear regression analysis was applied to evaluate the risk factor of core muscle loss in PD patients. RESULTS: Compared with controls, patients with PD had significantly higher thigh fat percentage and smaller gray matter volume of several brain locations of the default mode network (DMN), specifically the left superior temporal gyrus, right uncus, and left inferior temporal gyrus, revealing association with higher thigh fat percentage. Further multiple linear regression analysis indicated that higher thigh fat percentage is associated with gender (female), increased disease duration, and smaller gray matter volume of the left superior temporal gyrus and right uncus in PD patients. CONCLUSIONS: Patients with PD experience core muscle loss in the thigh, associated with default mode network (DMN) degeneration, longer disease duration, and female gender. Identification of risk factors associated with lean muscle mass loss may assist in early prevention of comorbidities such as sarcopenia.

Reduced lateral occipital gray matter volume is associated with physical frailty and cognitive impairment in Parkinson's disease.

INTRODUCTION: To investigate the structural changes of the brain that correlate with physical frailty and cognitive impairments in Parkinson's disease (PD) patients. METHODS: Sixty-one PD patients and 59 age- and sex-matched healthy controls were enrolled. For each participant, a frailty assessment using Fried's criteria and comprehensive neuropsychological testing using the Wechsler Adult Intelligence Scale-III and Cognitive Ability Screening Instrument were conducted, and structural brain MR images were acquired for voxel-based morphometric analysis. The neuropsychological testing includes various tests in these five domains: attention, executive, memory, speech and language, and visuospatial functions. Exploratory group-wise comparisons of gray matter volume (GMV) in the PD patients and controls were conducted. Voxel-wise multiple linear regression analyses were conducted for physical frailty-related and cognitive impairment-related GMV changes in the PD patients. Voxel-wise multiple linear regressions were also performed with the five cognitive domains separated using the same model. RESULTS: The PD patients exhibited diffuse GMV reductions in comparison to the controls. In the PD patients, physical frailty-related decreases in GMV were observed in the bilateral frontal and occipital cortices, while cognitive impairment-related decreases in GMV were observed in the bilateral frontal, occipital, and temporal cortices. These regions overlap in the lateral occipital cortex. After the five domains of cognitive functions were analyzed separately, physical frailty-related decreases in GMV still overlap in lateral occipital cortices with every domain of cognitive impairment-related decreases in GMV. CONCLUSION: Reduced GMV in the lateral occipital cortex is associated with cognitive impairment and physical frailty in PD patients. KEY POINTS: • Physical frailty in PD was associated with decreased GMV in the frontal and occipital cortices, while cognitive impairment was associated with decreased GMV in the frontal, temporal, and occipital cortices. • Physical frailty and cognitive impairment were both associated with decreased GMV in the lateral occipital cortex, which is part of the ventral object-based visual pathway. • Decreased GMV in the lateral occipital cortex may serve as a potential imaging biomarker for physical frailty and cognitive impairment in PD.

Reduced gray matter volume and respiratory dysfunction in Parkinson's disease: a voxel-based morphometry study.

BACKGROUND: The respiratory dysfunction of patients with Parkinson's disease (PD) has drawn increasing attention. This study evaluated the relationship between gray matter volume (GMV), as determined by voxel-based morphometry (VBM), and respiratory dysfunction in patients with PD and correlated it with systemic inflammatory markers. METHODS: Whole-brain VBM analysis was performed on 3-dimensional T1-weighted images in 25 PD patients with abnormal pulmonary function (13 men, 12 women; mean age: 62.9 ± 10.8 years) and, for comparison, on 25 sex- and age-matched PD patients with normal pulmonary function (14 men, 11 women; mean age: 62.3 ± 6.9 years). Inflammatory markers were determined by flow cytometry. The differences and correlations in regional GMV, clinical severity and inflammatory markers were determined after adjusting for age, gender and total intracranial volume (TIV). RESULTS: Compared with the normal pulmonary function group, the abnormal pulmonary function group had smaller GMV in several brain regions, including the left parahippocampal formation, right fusiform gyrus, right cerebellum crus, and left postcentral gyri. Forced expiratory volume in 1 s (FEV1) and maximal expiratory flow after expiration of 50% of forced vital capacity (MEF50) were positively correlated with regional GMV. There were no significant differences in the level of serum inflammatory markers between two groups. CONCLUSION: Our findings suggested that involvement of the central autonomic network and GM loss may underlie the respiratory dysfunction in PD patients.

Altered Striatocerebellar Metabolism and Systemic Inflammation in Parkinson's Disease.

Parkinson's disease (PD) is the most second common neurodegenerative movement disorder. Neuroinflammation due to systemic inflammation and elevated oxidative stress is considered a major factor promoting the pathogenesis of PD, but the relationship of structural brain imaging parameters to clinical inflammatory markers has not been well studied. Our aim was to evaluate the association of magnetic resonance spectroscopy (MRS) measures with inflammatory markers. Blood samples were collected from 33 patients with newly diagnosed PD and 30 healthy volunteers. MRS data including levels of N-acetylaspartate (NAA), creatine (Cre), and choline (Cho) were measured in the bilateral basal ganglia and cerebellum. Inflammatory markers included plasma nuclear DNA, plasma mitochondrial DNA, and apoptotic leukocyte levels. The Cho/Cre ratio in the dominant basal ganglion, the dominant basal ganglia to cerebellum ratios of two MRS parameters NAA/Cre and Cho/Cre, and levels of nuclear DNA, mitochondrial DNA, and apoptotic leukocytes were significantly different between PD patients and normal healthy volunteers. Significant positive correlations were noted between MRS measures and inflammatory marker levels. In conclusion, patients with PD seem to have abnormal levels of inflammatory markers in the peripheral circulation and deficits in MRS measures in the dominant basal ganglion and cerebellum.

Association Between Autonomic Impairment and Structural Deficit in Parkinson Disease.

Patients with Parkinson disease (PD) have impaired autonomic function and altered brain structure. This study aimed to evaluate the relationship of gray matter volume (GMV) determined by voxel-based morphometry (VBM) to autonomic impairment in patients with PD. Whole-brain VBM analysis was performed on 3-dimensional T1-weighted images in 23 patients with PD and 15 sex- and age-matched healthy volunteers. The relationship of cardiovascular autonomic function (determined by survey) to baroreflex sensitivity (BRS) (determined from changes in heart rate and blood pressure during the early phase II of the Valsalva maneuver) was tested using least-squares regression analysis. The differences in GMV, autonomic parameters, and clinical data were correlated after adjusting for age and sex. Compared with controls, patients with PD had low BRS, suggesting worse cardiovascular autonomic function, and smaller GMV in several brain locations, including the right amygdala, left hippocampal formation, bilateral insular cortex, bilateral caudate nucleus, bilateral cerebellum, right fusiform, and left middle frontal gyri. The decreased GMVs of the selected brain regions were also associated with increased presence of epithelial progenitor cells (EPCs) in the circulation. In patients with PD, decrease in cardiovascular autonomic function and increase in circulating EPC level are associated with smaller GMV in several areas of the brain. Because of its possible role in the modulation of the circulatory EPC pool and baroreflex control, the left hippocampal formation may be a bio-target for disease-modifying therapy and treatment monitoring in PD.

Safety and mutagenicity evaluation of nanoparticulate red mold rice.

Nowadays, people have recognized the importance of Monascus fermented products due to their many health benefits. A previous study demonstrated a novel formulation approach for the preparation of nanoparticulate red mold rice (NRMR). The aim of this study is to determine the useability of stable NRMR dispersion by evaluating its safety and mutagenicity with the Ames test. The crude red mold rice (RMR) was processed using a wet milling technology in the presence of distilled water to form an aqueous-based nanoparticle dispersion with a mean particle size of 259.3 nm. The formulated diepersion was found to be homogeneous and exhibited unimodal particle size distribution when analyzed by dynamic laser scattering techniques. Ames test results indicated that the equivalent of up to 1 mg of ethanol extract of RMR per plate exhibited no genotoxicity toward Salmonella typhimurium strains TA 98, TA 100, and TA 102. In the feeding toxicity test, the no observed adverse effect level (NOAEL) of NRMR was found to be 1000 mg/kg/day for both male and female rats. In conclusion, red mold rice can be formulated as a stable nanoparticulate dispersion using wet milling technology. In vitro and in vivo safety evaluations of NRMR indicated that no mutagenic or toxic responses were observed in this study.